Purine Nucleoside Phosphorylase Inhibition Blocks Bone Resorption in Periodontal Disease

Purine Nucleoside Phosphorylase (PNP) is an important enzyme of the purine salvage pathway that catalyzes the reversible phosphorolysis of purine nucleosides. T-CD4 lymphocytes, which play a key role in the pathogenesis of periodontal disease, heavily rely on PNP to avoid intracellular accumulation of dGTP and inhibition of ribonucleotide reductase, which, in turn, enables proliferation.

Objectives: To assess the effects of a pharmacological inhibitor of PNP (BCX-1777) in a model of chronic periodontal disease.

Methods: Wistar male rats (n=4) received BCX-1777 intraperitoneally and had silk ligatures tied around the right and left first molars. Additional doses were administered every two days until sacrifice (7th day). Control animals received the same volume of sterile saline. A third group that comprised animals that did not receive any treatment was used as a reference for the normal position of the bone relative to the CEJ and histomorphometric parameters (non-challenged control). The mandibles were processed for direct quantification of alveolar bone loss, histomorphometric analysis and osteoclast counting (TRAP).

Results: A marked loss of alveolar bone in the group treated with saline only was observed (60%). Animals treated with BCX-1777, on the other hand, presented abrogation of the bone loss induced by the ligatures, with no significant differences relative to non-challenged animals. The analyses also depicted clear effects over osteoclast numbers and inflammatory/immune cell subpopulations present in the periodontal tissues.

Conclusion: PNP exerts important roles in the control of cell subsets and processes involved in the bone resorbing activity triggered by chronic inflammation. BCX-1777, an analog of the transition state of PNP activity, holds great promise as a drug in the treatment of diseases characterized by imbalances of bone metabolism. Supported by CNPq and DECIT/SCTIE/Ministry of Health, Brasília, DF, Brazil.